Non-coding RNA in Liver Diseases

Non-coding RNA molecules are very numerous and have many regulatory functions, but have been studied very little. Our aim is to identify long non-coding RNA (lncRNA) implicated in different diseases, particularly liver diseases such as cirrhosis, liver cancer, and infection by the hepatitis C virus, and their treatment with interferon. In fact, we have already identified some lncRNA molecules whose expression is altered in some of these diseases.

We are currently determining whether these lncRNA molecules have a role in the onset or progression of these diseases, or whether they can be used to treat them. We also want to determine the molecular mechanisms that permit their function. Our longer-term goal is to apply the knowledge obtained to developing gene-therapy vectors that are susceptible to fine regulation mechanisms. We have already developed viral vectors that inhibit the expression of target genes by expressing short RNA molecules, such as siRNA, modified small nuclear RNA (snRNA) or both. These inhibitors are highly effective in cells in cultures and animal models.
Finally, in an independent line of work, we are also using viral vectors to express a growth factor similar to that of type-1 insulin (IGF-1) in cirrhotic livers. In the laboratory, we've shown that the expression of low levels of IGF-1 in the liver is capable of reverting liver cirrhosis. We aim to determine the molecular mechanisms that allow this therapeutic effect to take place and, if we obtain funding, we intend to carry out a clinical trial to evaluate the efficacy of this treatment in cirrhotic patients.

"We have developed viral vectors that inhibit the expression of target genes by expressing short RNA molecules, and which are very effective in cells in cultures and animal models", Dra. Puri Fortes, Principal Investigator.